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Tag: Faculty of Health and Medical Sciences

  • New Method Simplifies Identification of Right Treatment for Tabooed Disease Affecting Thousands

    New Method Simplifies Identification of Right Treatment for Tabooed Disease Affecting Thousands

    Newswise — Most people have at some point in their life suffered an intestinal infection or food poisoning forcing them to stay close to the bathroom. It is very uncomfortable. Most of the time, though, it passes quickly.

    But around 60,000-100,000 Danes suffer from a form of chronic diarrhoea called bile acid malabsorption or bile acid diarrhoea.

    It is a chronic condition characterised by frequent and sudden diarrhoea more than 10 times a day. Even though the disease is not life-threatening, it can seriously affect the patient’s everyday life, especially their social life, and be extremely disabling.

    “You have to rush to the bathroom several times a day. Therefore, keeping a job or maintaining social relations can be difficult, and a lot of people isolate themselves. The disease controls their life,” says Professor Jesper Bøje Andersen from the Biotech Research & Innovation Centre.

    He and his research group and clinical cooperation partners at Herlev and Gentofte Hospital headed by Professor and Consultant Doctor Filip Krag Knop are responsible for a new study, which provides new ways of diagnosing bile acid diarrhoea and identifying the most effective treatment for the individual patient.

    “A lot of people with chronic diarrhoea don’t realise that they suffer from bile acid diarrhoea and what has caused it. This is a result of lack of knowledge among healthcare workers and the relatively complex and expensive – and for the patient difficult – process of diagnosing the disease,” says Filip Krag Knop.

    Jesper Bøje Andersen adds:

    “We have developed a new concept which may be used to diagnose the disease based on a simple blood sample. Today, diagnostics involves radiopharmaceuticals, which means that there is a radiation risk. The process is not necessarily dangerous, but unpleasant and arduous, and not all countries in the world support the method, including the US.”

    The new method means that doctors should be able to determine whether the patient has bile acid diarrhoea based on a simple blood sample. They focus on molecules known as metabolites in the blood.

    “A blood sample contains lots of different metabolites. Right now we are able to identify almost 1,300 different metabolites, and around a handful of these can be used to diagnose bile acid diarrhoea. The metabolites of bile acid diarrhoea patients form a particular pattern that makes them recognisable,” says Jesper Bøje Andersen.

    Which treatment?

    The researchers analysed blood samples from 50 patients and they quickly realised that the samples – and patients – could be divided into two groups.

    “First, we did not understand why. All the blood samples had been taken before treatment, typically at the time of diagnosis,” says Jesper Bøje Andersen.

    The patients then participated in a randomised clinical study at the Center for Clinical Metabolic Research at Herlev and Gentofte Hospital. Here the doctors studied the effect of two different treatments: the conventional treatment involving bile acid sequestrant colesevelam and a new treatment involving liraglutide, which is normally used to treat type 2 diabetes and severe overweight.

    “What is interesting is that the metabolites in the patients’ blood divided them into two groups: one that responds well to colesevelam and one that responds well to liraglutide. This suggests that we should be able to say which treatment is the most effective by analysing the patient’s blood at the time of diagnosis,” says Jesper Bøje Andersen.

    The clinical study showed that colesevelam treatment eased the bile acid diarrhoea symptoms of 50 per cent of the patients, while liraglutide treatment eased the symptoms of 77 per cent of the patients.

    Jesper Bøje Andersen, Filip Krag Knop and their research groups hope the new study will benefit the 60,000-100,000 Danes who suffer from bile acid diarrhoea.

    The majority of cases of bile acid diarrhoea is diagnosed at a very late stage or never diagnosed at all.

    “Around 40 per cent of the patients suffer from this condition for up to five years before it is diagnosed. Of course, this may be because they do not realise that it is a disease and that it can be treated. But it may also be because chronic diarrhoea is a tabooed disease,” says Filip Krag Knop.

    You can read the study, “The Serum Lipidome Unravels a Diagnostic Potential in Bile Acid Diarrhea”, in Lewinska & Kårhus et al., GUT.

     

    About bile acid diarrhoea

    When we eat high-fat food, the gallbladder releases bile acid. Bile acid helps the body absorb fat and fat-soluble vitamins from the food. Around 98 per cent of the bile acid is absorbed by the small intestine and returned via the blood to the liver. If the body either produces and/or releases excessive amounts of bile acid or if the bile acid is not reabsorbed by the blood, a large amount will end up in the large intestine. Here it will result in irritated mucosa, lack of fluid in the intestines and increased intestinal movements, all of which create symptoms of bile acid diarrhoea.

    University of Copenhagen, Faculty of Health and Medical Sciences

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  • Resistant bacteria are a global problem. Now researchers may have found the solution

    Resistant bacteria are a global problem. Now researchers may have found the solution

    Newswise — Staphylococcus aureus. You may have had it in connection with a wound infection. In most cases, it will pass without treatment, while severe cases may require antibiotics, which kills the bacteria. This is the case for the majority of the population. In fact, many of us – though we feel perfectly fine – carry staphylococci in the nose, a good, moist environment in which the bacteria thrive.

    However, more and more staphylococci are becoming resistant to antibiotics (also known as multi resistant staphylococcus aureus or MRSA), and these infections can be difficult to treat.

    “Antibiotics resistance is an increasing problem, especially on a global scale. And when you have this relatively simple infection which suddenly cannot be treated with antibiotics, the situation can turn serious, sometimes life-threatening,” says Professor Niels Ødum from the LEO Foundation Skin Immunology Research Center at the University of Copenhagen.

    Therefore, all over the world, a lot of resources are being invested in fighting antibiotics resistance in staphylococcus aureus infections, and a new study among skin lymphoma patients has produced positive results. A new substance called endolysins has proven capable of killing both resistant and non-resistant staphylococcus aureus – without the need for antibiotics. But we will get back to that.

    The discovery is good news to patients with a weak immune system to whom a staphylococcus aureus infection can be serious and, at worst, fatal. But it also adds to the knowledge we have of other forms of treatment.

    “To people who are severely ill with e.g. skin lymphoma, staphylococci can be a huge, sometimes insoluble problem, as many are infected with a type of staphylococcus aureus that is resistant to antibiotics,” says Niels Ødum and adds:

    “That is why we are careful not to give antibiotics to everyone, because we do not want to have to deal with more resistant bacteria. Therefore, it is important that we find new ways of treating – and not the least to prevent – these infections.”

    New substance may be the answer

    In some patients, a staphylococcus aureus will cause the cancer to worsen. And even though antibiotics appear to work in some cases, it is not without its problems.

    “We can tell that giving high doses of antibiotics to patients with serious infections causes their health, skin and cancer symptoms to improve. But once we stop giving them antibiotics, the symptoms and staphylococci quickly return. Patients experience many adverse effects, and some risk getting resistant bacteria,” says Niels Ødum.

    Therefore, treating staphylococcus aureus can be tricky. At worst, cancer patients may die of an infection which doctors are unable to treat.

    And this is where endolysins enter the scene, as this new substance may be part of the solution to antibiotics resistance like MRSA.

    “This particular endolysin is a brand new, artificially produced enzyme that has been improved several times and designed as a new drug,” explains Postdoc Emil Pallesen, who is first author of the study. He adds:

    “The great thing about this enzyme is that it has been designed to penetrate the wall of staphylococcus aureus. This enables it to target and kill the harmful staphylococcus and leave harmless skin bacteria unharmed.”

    And that is what made the researchers decide to test the new substance; they expected it to be able to kill both resistant and non-resistant staphylococcus bacteria.

    “We have been testing the substance on skin samples from patients, and it does appear to kill staphylococcus aureus from patients. Endolysins do not care whether the bacterium is resistant to antibiotics or not, because it does not work in the same way as antibiotics,” says Niels Ødum and adds:

    “The really good news is that our lab tests have showed that endolysins do not just eradicate staphylococcus aureus; they also inhibit their ability to promote cancer growth.”

    The study, “Endolysin inhibits skin colonization by patient-derived Staphylococcus aureus and malignant T cell activation in cutaneous T cell lymphoma”, is published in the Journal of Investigative Dermatology.

    University of Copenhagen, Faculty of Health and Medical Sciences

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  • More than two billion are infected with this disease; Vitamin D can help

    More than two billion are infected with this disease; Vitamin D can help

    Newswise — Sarcomas are cancer tumours found in e.g. the bones, muscles or fatty tissue. It is a rare type of cancer seen in only one per cent of cancer patients. It is complex and difficult to treat.

    However, a new study may have found a new treatment that can help the sickest sarcoma patients.

    “We have learned that sarcoma patients whose cancer cells have a high expression of the cep135 protein are worse off. But inhibiting a gene called plk1 also inhibits growth of the sarcoma cells, and this suggests that we can target the treatment of the sickest sarcoma patients,” says Associate Professor Morten Scheibye-Knudsen from the Center for Healthy Aging at the Department of Cellular and Molecular Medicine, who is responsible for the new study.

    Methods for identifying sarcoma patients’ prognoses are already available, as are different forms of treatment. But the new study has identified a new method.

    “This is a new way of stratifying and possibly a new and better way of treating sarcoma. And the introduction of yet another method is always good news to patients. Because no two cancers are alike. Ideally, treatment should always be tailored to the individual patient,” Morten Scheibye-Knudsen stresses.

    He hopes other researchers with access to the necessary test facilities will study his results in more detail and eventually design a new treatment. If the method turns out to work, he believes a new treatment may be available to patients in five to 10 years.

    Grey hair, wrinkles and loss of fatty tissue at an early age

    Morten Scheibye-Knudsen and his colleagues started out by studying patients suffering from the rare neurological disorders Werner’s syndrome, Nijmegen breakage syndrome and Ataxia-telangiectasia syndrome.

    These patients experience symptoms of early ageing such as grey hair, wrinkles and loss of fatty tissue – and they have a high risk of developing cancer at an early age.

    “Age-associated diseases such as cancer is one of my main areas of interest as a researcher at the Center for Healthy Aging. As we grow older, a lot of things happen to the body, and determining causality can be difficult. But in people suffering from e.g. Werner’s syndrome it is easier to see which genes are responsible for which processes. This gives us a molecular handle, so to speak,” says Morten Scheibye-Knudsen.

    In order to establish why these patients develop cancer at an early age, the researchers compared gene expressions across the three disorders. Here they worked together with the company Insilico Medicine, whose large Pandaomics platform made it possible to identify gene mutations in thousands of different disorders. It turned out that cep135 is a common denominator for the cancer genes of the three disorders.

    “This made us study the gene expressions of various cancers, and we learned that cep135 is associated with high mortality in i.a. sarcoma, but also in bladder cancer. Sarcoma was particularly interesting, as many Werner’s syndrome patients develop sarcoma,” explains Morten Scheibye-Knudsen.

    Finally, the researchers sought to find ways to inhibit the sarcoma. Cep135 is not a useful target, as it is a so-called structural protein, which are difficult to target. Instead, the researchers learned that by inhibiting the plk1 gene they were able to target the sarcoma.

    “The study indicates that we can use genetic diseases that exhibit accelerated aging to identify new treatment targets. In this study, we investigated cancer, but the method can in principle be used for all age-related diseases such as dementia, cardiovascular diseases and others,” says Morten Scheibye-Knudsen.

    Read the entire study, ”High-confidence cancer patient stratification through multiomics investigation of DNA repair disorders”, in CDDpress.

    What are sarcomas?

    Sarcomas are cancer tumours found in i.a. the bones, muscles or fatty tissue. There are two main types: bone sarcoma and soft tissue sarcoma (muscles, fatty tissue, connective tissue, blood vessels and neurilemma).

    Sarcoma affects one per cent of cancer patients. In Denmark, around 45 people are diagnosed with bone sarcoma each year and 220 with soft tissue sarcoma. Adults diagnosed with bone sarcoma have a 60-per cent five-year survival rate, while adults diagnosed with bone sarcoma have a 50-70-per cent five-year survival rate.

    University of Copenhagen, Faculty of Health and Medical Sciences

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